西南师范大学学报（自然科学版）
西南師範大學學報（自然科學版）
서남사범대학학보（자연과학판）
JOURNAL OF SOUTHWEST CHINA NORMAL UNIVERSITY
2014年
4期
105-112
,共8页
重组细胞%微粒体%细胞色素P4503A4%细胞色素P4503A22%药物代谢
重組細胞%微粒體%細胞色素P4503A4%細胞色素P4503A22%藥物代謝
중조세포%미립체%세포색소P4503A4%세포색소P4503A22%약물대사
recombinant cell line%microsome%cytochrome P4503A4%cytochrome P4503A22%pharmacoki-netics
目的：利用已建立的巴马小型猪细胞色素 P4503A22和 P4503A4稳定表达重组肝癌细胞株微粒体,分析比较二者的药物代谢动力学特征.方法：以P4503A特异性代谢底物硝苯地平(NF)、睾酮及其抑制剂酮康唑(KCZ)为探针药物,将探针药物与重组P4503A4,P4503A22细胞微粒体在优化的微粒体浓度、药物浓度、孵育时间等条件下进行体外孵育,通过高效液相色谱仪检测其药物代谢(抑制)动力学参数,并将二者进行比较分析.结果：P4503A22的硝苯地平、睾酮的代谢活性均低于P4503A4(p<0.05)；酮康唑对P4503A4和P4503A22的硝苯地平代谢具有较强的抑制活性,但酮康唑对P4503A4的抑制活性强于 P4503A22(p<0.05).结论：无论是代谢底物或抑制底物活性,重组P4503A22细胞微粒体活性均低于重组P4503A4细胞微粒体活性.
目的：利用已建立的巴馬小型豬細胞色素 P4503A22和 P4503A4穩定錶達重組肝癌細胞株微粒體,分析比較二者的藥物代謝動力學特徵.方法：以P4503A特異性代謝底物硝苯地平(NF)、睪酮及其抑製劑酮康唑(KCZ)為探針藥物,將探針藥物與重組P4503A4,P4503A22細胞微粒體在優化的微粒體濃度、藥物濃度、孵育時間等條件下進行體外孵育,通過高效液相色譜儀檢測其藥物代謝(抑製)動力學參數,併將二者進行比較分析.結果：P4503A22的硝苯地平、睪酮的代謝活性均低于P4503A4(p<0.05)；酮康唑對P4503A4和P4503A22的硝苯地平代謝具有較彊的抑製活性,但酮康唑對P4503A4的抑製活性彊于 P4503A22(p<0.05).結論：無論是代謝底物或抑製底物活性,重組P4503A22細胞微粒體活性均低于重組P4503A4細胞微粒體活性.
목적：이용이건립적파마소형저세포색소 P4503A22화 P4503A4은정표체중조간암세포주미립체,분석비교이자적약물대사동역학특정.방법：이P4503A특이성대사저물초분지평(NF)、고동급기억제제동강서(KCZ)위탐침약물,장탐침약물여중조P4503A4,P4503A22세포미립체재우화적미립체농도、약물농도、부육시간등조건하진행체외부육,통과고효액상색보의검측기약물대사(억제)동역학삼수,병장이자진행비교분석.결과：P4503A22적초분지평、고동적대사활성균저우P4503A4(p<0.05)；동강서대P4503A4화P4503A22적초분지평대사구유교강적억제활성,단동강서대P4503A4적억제활성강우 P4503A22(p<0.05).결론：무론시대사저물혹억제저물활성,중조P4503A22세포미립체활성균저우중조P4503A4세포미립체활성.
Obj ective:To compare the pharmacokinetic characteristics of two microsomes prepared from the recombinant cell lines cytochrome P4503A22 and cytochrome P4503A4.Methods:NF (nifedipine)and TST (testosterone),which are the substrates of the specific metabolism of P4503A,and their inhibitor KCZ (ketoconazole)were used as the probe drugs and incubated in vitro with the microsomes prepared from the recombinant cell lines HepG2-P4503A4 and HepG2-P4503A22 under optimal conditions (micro-some concentration,drug concentration and incubation time).HPLC (high performance liquid chromatog-raphy)was utilized to detect the metabolites after incubation,and the pharmacokinetic characteristics were analyzed based on the experimental data.Results:The metabolic activities of cytochrome P4503A22 to both nifedipine and testosterone were lower than those of cytochrome P4503A4 (p<0.05).Ketoconazole showed a strong inhibitory activity to both cytochromes,but the inhibitory activity to P4503A4 was stron-ger than that to P4503A22 (p<0.05).Conclusion:P4503A4 has a stronger substrate metabolic activity and inhibitory activity than P4503A22.
